Results from an Ongoing Open Phase 2 Study Assessing the Safety, Efficacy and Pharmacological Effects of Bromelain-based Enzymatic Debridement on Biofilm, Microbial loads and Cytokines in patients with DFU and VLU

IntroductionDebridement represents a key step in the management of chronic wounds and is considered a basic necessity to induce tissue repair. Biofilm infection in wounds is a major contributor to increased morbidity, delayed healing, persistent infections, and greater economic burden. Use of novel therapies that specifically remove the necrotic tissues, reduce bioburden and promote biofilm dispersion is a promising strategy for improving patient outcomes. Bromelain-based enzymatic debridement agent (BBD) is currently in clinical development for debridement of chronic wounds. Study objectives are to assess its safety, efficacy and pharmacological effects in up to 15 patients with venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). MethodsSeven DFU and VLU patients were enrolled to a prospective, open label, single-arm phase 2 study. Patients were treated with up to 8 daily applications of BBD and then continued follow-up for 2 weeks. Punch biopsies (3.0mm) and wound fluids were collected prior to the first and after last treatment for evaluation of biofilm presence and biomarkers of wound healing and inflammation, respectively. Fluorescence imaging device was used during treatment to measure bacterial load ( >104CFU/g). Red and cyan fluorescence are associated with bacterial loads. Fluorescence imaging was also utilized to identify the highest fluorescence area to obtain the biopsy.ResultsFour DFU and 2 VLU patients completed treatment (one patient discontinued). In 4/6 patients 89-100% Non-Viable Tissue was removed within 2-8 applications. Additionally, an average reduction of in wound size was measured by the end follow-up period: 7.4 cm2 at baseline vs. 4.7 cm2 at the end of follow-up. In 4 patients who were positive for biofilm at baseline, the biofilm was reduced to single individual microorganisms or not detected by the end of treatment. Average±SEM red fluorescence (e.g. Staphylococcus aureus) reduced from 1.52±0.97 cm2 pre-treatment to 0.64±0.41 cm2 post treatment, and in one patient cyan fluorescence (Pseudomonas aeruginosa) reduced from 5.95 cm2 to zero. Safety data show that BBD is safe and well tolerated. DiscussionThe data shows that BBD is safe and can effectively debride wounds and promote wound area reduction while reducing biofilm and bacterial bioburden.